Muscular dystrophies are a heterogeneous group of disorders characterized by muscle weakness and wasting. Current treatments of this kind of pathologies consist in clinical management of symptoms.
However, for the most common muscular dystrophy, Duchenne dystrophy, several promising strategies are emerging. Particularly, the exon skipping therapy has shown hopeful results in the effective treatment and regeneration of dystrophic muscle.
Dysferlinopathies are autosomal recessive diseases of the group of muscular dystrophies comprising Limb Girdle Muscular Dystrophy type 2B and Miyoshi myopathy. Dysferlinopathies are caused by mutations in the DYSF gene located in the chromosome region 2p13.1-13.3. This gene includes 55 exons in its most characterized form (GenBank NM—003494.2), and different isoforms through the existence of alternative exons 1 of DYSF-v1 (GenBank DQ267935), exon 5a (GenBank DQ976379) and exon 40a (GenBank EF015906). The DYSF gene encodes the dysferlin protein, which is implicated in sarcolemmal repair. There are currently no real treatments for these dysferlinopathies whereas only symptoms are managed.
In 2006, Sinnreich et al. reported a patient case presenting a particularly mild phenotype of dysferlinopathy. This patient was the mother of two severely affected sisters, both homozygous for a dysferlin null mutation. Their mother was a compound heterozygous for the same null mutation, and, in addition, carried a lariat branch point mutation in intron 31 leading to an in-frame skipping of exon 32. Because she presented with only a mild proximal weakness and remained ambulant even after 70 years of age, it is most likely that the exon 32 skipped-allele may partially complement the null mutation in trans.